Can mitochondrial function predict response to radiation therapy for rectal cancer?

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Project Summary and Overview Rationale and Background Information Mitochondria are known to perform important cellular functions including energy production and regulation of cell death, and are also affected by ionising radiation. There is evidence to suggest that the level of mitochondrial activity has a role in the response to radiotherapy for malignancy. Rectal cancer has a highly variable response to neoadjuvant radiotherapy, and while there are some known factors associated with the degree of response, there no robust markers that can predict it. The development of such a marker could potentially allow more targeted use of neoadjuvant radiotherapy for rectal cancer, thereby avoiding associated morbidity in patients unlikely to benefit. Objectives This study aims to determine whether the level of mitochondrial function within the tumour cells is associated with tumour regression after radiotherapy for rectal cancer. Methods This is an observational pilot study. Patients with rectal cancer will undergo colonoscopy and have biopsies of both tumour tissue and normal appearing rectal mucosa. Surrogates of mitochondrial function will be measured using the Western Blot technique, with a panel of ten proteins representative of mitochondrial activity being assessed. Routine loco-regional staging with MRI of the pelvis will be performed before treatment. After radiotherapy and surgical resection, repeat testing of the tumour tissue and adjacent rectal mucosa will be performed to assess for changes in mitochondrial function after treatment with radiotherapy. A tumour regression grade (TRG) will be recorded for each patient based on the final pathology of the resection specimen. Correlation between markers of mitochondrial activity and tumour regression will be assessed. Population and timeframe All patients diagnosed with rectal cancer and treated with neoadjuvant radiotherapy at Christchurch Hospital for a 12 month period from February 1 2018. Five patients not treated with radiotherapy will also be included to act as a control group. Expected outcomes The markers of mitochondrial activity will be examined in an attempt to identify those which correlate with the TRG. The results may be used to guide further investigation of a specific biomarker(s).

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